Several previous studies have reported the relationship between POCs and long-term survival in gastric cancer, however, the results still remain controversial [11, 15–17, 20–23, 30–36]. Additionally, these studies failed to exclude patients who died in a short postoperative period. Of note, POCs increase the early mortality, which would overshadow the real influence of complications on long-term survival of cancer patients [37, 38]. In the present study, 1667 GC patients with curative resection were analyzed and 17.10% of them occurred POCs C-D ≥ II (excluding deaths within 90 days after surgery). Older age, comorbidities, extensive lymph node dissection and perioperative blood transfusion were associated with a high incidence of POCs. With respect to the relationship of complication and survival, we revealed (1) that occurrence of POCs was indeed significantly associated with shortened long-term OS, (2) ICs were the mainly driver for poor survival instead of NICs, (3) among all complications, pulmonary infection in this study was the greatest risk factor for the decreased OS.
The influence of POCs, particularly ICs, on long-term survival has been described in several types of cancer [11–13].Recently, in a systematic review and meta-analysis about the effect of POCs on long-term survival in patients with curative gastrectomy, Wang et al. identified a 40% higher risk of death in patients with POCs and a much higher (86%) mortality risk in patients with ICs compared with those without, respectively , which was in line with our results. Similarly, in lung cancer, a similar outcome reported by Andalib et al. have also demonstrated that major ICs were the main reason for worse long-term survival and NICs had a minor effect on this bad outcome, excluding early deaths .
With respect to the mechanism of presence of complications on poor survival, Accumulated evidences [17, 40, 41] had indicated that the surgical stress, especially in major surgery, would induce body inflammatory response which could be enhanced and prolonged by POCs. It’s also well established that postoperative inflammatory response has a contribution on host immunosuppression by mainly suppressing cell-mediated immunity [42,43], especially natural killer cells and cytotoxic T lymphocytes are compromised , which promotes the proliferation and metastasis of residual tumor cells. Furthermore, numerous researches have confirmed that ICs have a direct effect on cancer cell metastatic ability by activating bacterial antigen-mediated processes [44, 45]. Indeed, in our study, a remarkable difference in overall survival between patients stratified by presence of complication in p-Stage III is likely to reflect the quantity of residual tumor cells which would cause early recurrence.
Nevertheless, we have to admit that whether POCs have a direct cause-effect relationship on shortened survival is still not very clear. Alternatively, the pernicious effect of postoperative complications on long-term survival could be just a confounder, such as surgical technique, may be the reason for both occurrence of POCs and decreased long-term survival. What we can conclude in our study is that POCs have an influence on poor prognosis. Considering the curability of the POCs and its potential benefit on the long-term survival, it’s worthy and crucial to prudently deal with POCs with active intervention and remediation. Meanwhile, for patients at risk of occurrence of POCs, such as those with older age, presence of comorbidities, extensive lymphadenectomy and perioperative blood transfusion, more attention should be paid to.
The limitations of our study were its retrospective nature and presence of several confounding factors. And there was a lack of enough information about adjuvant chemotherapy, for example, the starting time of adjuvant chemotherapy among patients was not clear, which may have an effect on survival considering delayed chemotherapy is detrimental to prognosis. Another limitation was the inability to calculate DFS because its potential difficulty to get the precise recurrence time of these cancer patients in such a large population cohort. Despite these limitations, we believe that postoperative complications are an important prognostic factor.
In conclusion, postoperative complications after curative resection of gastric cancer are common and are associated with poor overall survival in gastric cancer patients. The risk is mainly driven by infectious complications (especially pulmonary infection) rather than noninfectious complications. Based on our findings, meticulous surgery is needed and prudent medical intervention in patients with complications is also compulsory to increase the long-term survival of gastric cancer patients.